The present invention relates to a series of new thiazolidinone and oxazolidinone derivatives containing a nitrooxyalkylcarbamoyl group, and provides methods and compositions using these compounds as vasodilators, e.g. in the therapy and prophylaxis of cardiovascular diseases; the invention also provides processes for their preparation.
Cardiovascular diseases are a well known and increasing cause of death and disability in the world, and considerable efforts have been expended in a search for drugs capable of treating or preventing such diseases.
Nitroglycerin is frequently used, and has been used for many years, for the therapy of cardiovascular diseases, particularly angina pectoris, but this compound has several disadvantages when used as a medicine. For example, the compound is easily inactivated in the liver (the "first-pass effect") and the duration of the effect is very short. Furthermore, the medicine sometimes causes adverse reactions, such as cephalalgia, vertigo and tachycardia, as a result of its reducing the patient's blood pressure. It has, therefore, been desired for many years to discover anti-anginal drugs showing a long lasting effect but which do not have the problem of the first-pass effect.
We have now discovered a series of compounds which we believe achieve this aim.
The closest prior art to the compounds of the present invention is believed to be U.S. Pat. No. 4 200 640, which describes a number of compounds including N-(2-nitrooxyethyl)-3-pyridinecarboxamide, which is said to have activity as a coronary vasodilator.
The compounds of the present invention resemble the prior art compound in having a nitrooxyalkylcarbamoyl group, but differ in that they include a thiazolidinone or oxazolidinone group. These compounds also have vasodilatory activity, and, because they have few adverse effects, they are expected to be of use for the treatment and prophylaxis of cardiovascular disorders or insufficiency, such as angina pectoris.